Pioneering Patient-Specific Approaches for Precision Surgery Using Imaging and Virtual Reality.

Endovascular treatment of complex vascular anomalies shifts the risk of open surgical procedures to the benefit of minimally invasive endovascular procedural solutions. Complex open surgical procedures used to be the only option for the treatment of a myriad of conditions like pulmonary and aortic valve replacement as well as cerebral aneurysm repair. However, due to advancements in catheter-delivered devices and operator expertise, these procedures (along with many others) can now be performed through minimally invasive procedures delivered through a central or peripheral vein or artery. The decision to shift from an open procedure to an endovascular approach is based on multi-modal imaging, often including 3D Digital Imaging and Communications in Medicine (DICOM) imaging datasets. Utilizing these 3D images, our lab generates 3D models of the pathologic anatomy, thereby allowing the pre-procedural analysis necessary to pre-plan critical components of the catheterization lab procedure, namely, C-arm positioning, 3D measurement, and idealized road-map generation. This article describes how to take segmented 3D models of patient-specific pathology and predict generalized C-arm positions, how to measure critical two-dimensional (2D) measurements of 3D structures relevant to the 2D fluoroscopy projections, and how to generate 2D fluoroscopy roadmap analogs that can assist in proper C-arm positioning during catheterization lab procedures.

The paradox of tPA in ischemic stroke: tPA knockdown following recanalization improves functional and histological outcomes.

Previous studies have demonstrated that endogenous tissue-type plasminogen activator (tPA) is upregulated in the brain after an acute ischemic stroke (AIS). While mixed results were observed in genetic models, the pharmacological inhibition of endogenous tPA showed beneficial effects. Treatment with exogenous recombinant tPA exacerbated brain damage in rodent models of stroke. Despite the detrimental effects of tPA in ischemic stroke, recombinant tPA is administered to AIS patients to recanalize the occluded blood vessels because the benefits of its administration outweigh the risks associated with tPA upregulation and increased activity. We hypothesized that tPA knockdown following recanalization would ameliorate sensorimotor deficits and reduce brain injury. Young male and female rats (2-3 months old) were subjected to transient focal cerebral ischemia by occlusion of the right middle cerebral artery. Shortly after reperfusion, rats from appropriate cohorts were administered a nanoparticle formulation containing tPA shRNA or control shRNA plasmids (1 mg/kg) intravenously via the tail vein. Infarct volume during acute and chronic phases, expression of matrix metalloproteinases (MMPs) 1, 3, and 9, enlargement of cerebral ventricle volume, and white matter damage were all reduced by shRNA-mediated gene silencing of tPA following reperfusion. Additionally, recovery of somatosensory and motor functions was improved. In conclusion, our results provide evidence that reducing endogenous tPA following recanalization improves functional outcomes and reduces post-stroke brain damage.

Treatment-Resistant Depression With Catatonia Presenting as a Feature of Creutzfeldt-Jakob's Disease.

A high-functioning middle-aged successful businessman developed a rapid decline in his cognitive, behavioral, and motor abilities within one year. He was initially diagnosed with dementia by a neurologist and was then diagnosed with pseudo-dementia secondary to major depressive disorder with catatonia by a psychiatrist who initiated treatment with Ativan. He was referred to our psychiatric facility for an evaluation to undergo electroconvulsive therapy (ECT) as a potential treatment for medically refractory depression complicated with catatonia and pseudo-dementia. The neurology team and internal medicine team were consulted by a psychiatrist for clearance to begin a course of ECT. In this process, with a coordinated effort and prompt workup and evaluation, including neurological testing, imaging, and positive cerebrospinal fluid analysis for real-time quaking inverse conversion (RT-QuIC) and 14-3-3, the patient was diagnosed with Creutzfeldt-Jakob's disease. There are many organic causes of dementia and catatonia that should be explored in depth, especially when the clinical picture is challenging and atypical.

Effect of Known Atrial Fibrillation and Anticoagulation Status on the Prehospital Identification of Large Vessel Occlusion.

INTRODUCTION: The Cincinnati Prehospital Stroke Severity scale (C-STAT), Los Angeles Motor Scale (LAMS), Rapid Arterial Occlusion Evaluation (RACE) score, and Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scales were designed to aid emergency responder identification of patients with stroke related to large vessel occlusion (LVO). We hypothesized that the addition of a known history of atrial fibrillation (AF) without anticoagulation to currently used scales would improve LVO detection. METHODS: Medical records of patients admitted to a Comprehensive Stroke Center with acute ischemic stroke in 2014-2015 were reviewed. LVO identification using the C-STAT, LAMS, RACE, and FAST-ED scores and the AF variable were compared using univariable analyses. The areas under the receiver operating curves (AUCs) were then compared for each score, the AF variable, and each score with the addition of the AF variable. RESULTS: The sample included 233 patients without and 188 patients with an LVO. A history of known AF, history of AF with no anticoagulation, and the C-STAT, LAMS, RACE, and FAST-ED scores were each associated with LVO in univariable analyses. The AUCs for C-STAT, LAMS, RACE, and FAST-ED were similar. The addition of the known AF and no anticoagulation variable did not appreciably change these AUCs. CONCLUSION: Although known AF with no anticoagulation was associated with LVO in patients with acute ischemic stroke, this historic feature did not improve the accuracy of existing LVO detection scales.

Aseptic Meningitis and Depression: The Neuropsychiatric Manifestations of a Patient with Systemic Lupus Erythematosus.

Aseptic meningitis as an initial and isolated manifestation of systemic lupus erythematosus (SLE) is extremely rare. About a third of patients with SLE have neuropsychiatric manifestations; however, less than 2% develop aseptic meningitis. Therefore, SLE as a cause of aseptic meningitis is commonly overlooked and leads to delayed or even missed diagnosis. We report a case of aseptic meningitis that was later discovered to be SLE and where instituting appropriate treatment led to clinical improvement.

Secular Increases in Spontaneous Subarachnoid Hemorrhage during Pregnancy: A Nationwide Sample Analysis.

IMPORTANCE: Understanding of the epidemiology, outcomes, and management of spontaneous subarachnoid hemorrhage (sSAH) during pregnancy is limited. Small, single center series suggest a slight increase in morbidity and mortality. OBJECTIVE: To determine if incidence of sSAH in pregnancy is increasing nationally and also to study the outcomes for this patient population. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed utilizing the Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project for the years 2002-2014 for sSAH hospitalizations. The NIS is a large administrative database designed to produce nationally weighted estimates. Female patients age 15-49 with sSAH were identified using the International Classification of Diseases, 9th Revision, Clinical Modification code 430. Pregnancy and maternal diagnosis were identified using pregnancy related ICD codes validated by previous studies. The Cochran-Armitage trend test and parametric tests were utilized to analyze temporal trends and group comparisons. Main Outcomes and Measures: National trend for incidence of sSAH in pregnancy, age, and race/ethnicity as well as associated risk factors and outcomes. RESULTS: During the time period, there were 73,692 admissions for sSAH in women age 15-49 years, of which 3978 (5.4%) occurred during pregnancy. The proportion of sSAH during pregnancy hospitalizations increased from 4.16 % to 6.33% (P-Trend < .001) during the 12 years of the study. African-American women (8.19%) and Hispanic (7.11%) had higher rates of sSAH during pregnancy than whites (3.83%). In the NIS data, the incidence of sSAH increased from 5.4/100,000 deliveries (2002) to 8.5/100,000 deliveries (2014; P-Trend < .0001). The greatest increase in sSAH was noted to be among pregnant African-American women from (13.4 [2002]) to (16.39 [2014]/100,000 births). Mortality was lower in pregnant women (7.69% versus 17.37%, P < .0001). Pregnant women had a higher likelihood of being discharged to home (69.78% versus 53.66%, P < .0001) and lower likelihood of discharge to long term facility (22.4% versus 28.7%, P < .0001) than nonpregnant women after sSAH hospitalization. CONCLUSIONS AND RELEVANCE: There is an upward trend in the incidence of sSAH occurring during pregnancy. There was disproportionate increase in incidence of sSAH in the African American and younger mothers. Outcomes were better for both pregnant and nonpregnant women treated at teaching hospitals and in pregnant women in general as compared to nonpregnant women.

ACDD4 score: A simple tool for assessing risk of pneumonia after stroke.

BACKGROUND: Pneumonia is a serious but a preventable stroke complication. Prediction scales for post-stroke pneumonia have been proposed with an intent to improve surveillance and prevention but they remain under-utilized in clinical practice. Most existing scales were developed using both ventilated and non-ventilated patients which may affect their accuracy. We derived and validated a novel, pragmatic scale to predict hospital-acquired pneumonia (HAP) after stroke employing only a non-ventilated stroke cohort. METHODS: All consecutive patients admitted with acute stroke to a large hospital in Boston, Massachusetts, were identified using International Classification of Diseases, 9th revision (ICD-9) codes for acute ischemic strokes, intracerebral hemorrhages and confirmed by chart review. The following exclusion criteria were used: stroke occurring after hospitalization, pneumonia on admission, intubation, presence of brain or lung neoplasms, admission<48hours duration. HAP was defined using discharge ICD-9 codes. The association of relevant covariates with HAP was analyzed using multivariable stepwise logistic regression analysis to develop a scoring system and validated using bootstrapping. RESULTS: A total of 1644 patients met study criteria; 144 (8.8%) developed HAP. An 8-point pneumonia prediction scale (ACDD4) was derived using significant covariates (age≥75=1; congestive heart failure=1; dysarthria=1; dysphagia=4). The risk of pneumonia varied between 2% and 33.9% with scores of 0 to 7, respectively. The c-statistic of the final model was 0.82 and bootstrap validation c-statistic was 0.81. CONCLUSION: ACDD4 scale is a promising tool for predicting HAP in non-ventilated stroke patients that can be easily computed at the patient's bedside. Subject term: cerebrovascular disease/stroke.

Acid-suppressive medication use in acute stroke and hospital-acquired pneumonia.

OBJECTIVE: Pneumonia is a morbid complication of stroke, but evidence-based strategies for its prevention are lacking. Acid-suppressive medications have been associated with increased risk for nosocomial pneumonia in hospitalized patients. It is unclear whether these results can be extrapolated to stroke patients, where other factors strongly modulate pneumonia risk. We investigated the association between acid-suppressive medication and hospital-acquired pneumonia in patients with acute stroke. METHODS: All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage in a large, urban academic medical center in Boston, Massachusetts from June 2000 to June 2010 who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Acid-suppressive medication use was defined as any pharmacy charge for a proton-pump inhibitor or histamine-2 receptor antagonist. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: The cohort comprised 1,676 admissions. Acid-suppressive medication was ordered in 1,340 (80%) and hospital-acquired pneumonia occurred in 289 (17.2%). The unadjusted incidence of hospital-acquired pneumonia was higher in the group exposed to acid-suppressive medication compared to those unexposed (20.7% vs 3.6%, odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.9-12.7). After adjustment, the OR of hospital-acquired pneumonia in the exposed group was 2.3 (95% CI = 1.2-4.6). The association was significant for proton-pump inhibitors (OR = 2.7, 95% CI = 1.4-5.4), but not for histamine-2 receptor antagonists (OR = 1.6, 95% CI = 0.8-3.4). INTERPRETATION: In this large hospital-based cohort of patients presenting with acute stroke, acid-suppressive medication use was associated with increased odds of hospital-acquired pneumonia.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. METHODS: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Recovery of swallowing after dysphagic stroke: an analysis of prognostic factors.

BACKGROUND: Dysphagia is a major complication of stroke, but factors influencing its recovery are incompletely understood. The goal of this study was to identify important prognostic variables affecting swallowing recovery after acute ischemic stroke. METHODS: We retrospectively reviewed our patient database to identify acute ischemic stroke patients who developed dysphagia after stroke but were free of other confounding conditions affecting swallowing. Of the 1774 patients screened, 323 met the study criteria. We assessed the effect of age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, level of consciousness (LOC), facial weakness, dysarthria, neglect, bihemispheric infarcts, right hemispheric infarcts, brainstem infarcts, intubation, aspiration, acute stroke therapies, occurrence of symptomatic hemorrhagic transformation, seizures, pneumonia, and length of hospitalization (LOH) on persistence of dysphagia at hospital discharge in a logistic regression analysis. RESULTS: The mean age and NIHSS scores (mean ± standard deviation) were 75.9 ± 13.6 years and 13.5 ± 6.9, respectively; 58.5% were women. In a multivariate analysis, aspiration detected on a clinical swallowing evaluation (odds ratio [OR] 21.83; 95% confidence interval [CI] 8.16-58.42; P < .0001), aspiration on videofluoroscopic swallowing study (OR 10.50; 95% CI 3.35-32.96; P < .0001), bihemispheric infarcts (OR 3.72; 95% CI 1.33-10.43; P = .0123), dysarthria (OR 3.4; 95% CI 1.57-7.35; P = .0019), intubation (OR 2.86; 95% CI 1.10-7.39; P = .0301), NIHSS score ≥12 (OR 2.51; 95% CI 1.19-5.23; P = .0157) were significant predictors of persistent dysphagia. The area under the curve and Somer's Dxy statistics of the model were 0.8918 and 0.78, respectively, indicating good calibration and discriminative power. CONCLUSIONS: Prognostic factors affecting swallowing recovery identified in this study can help advance dysphagia research methodologies and the clinical care of stroke patients.

Therapeutic advances in understanding pathophysiology and treatment of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis is an important cause of stroke in young population. A thorough understanding of its pathophysiology, clinical, and radiological features is needed for an early and timely diagnosis to initiate appropriate treatment before the disease becomes worse and difficult to manage. In this study, the recent advances in the therapeutics of cerebral venous thrombosis with brief overview of epidemiology, clinical features, and imaging modalities were reviewed. With emerging imaging modalities and therapeutic options, there has been a progress in ease of ability to diagnose and treat cerebral venous thrombosis, but because of the lack of a much-needed randomized controlled trial, there is deficiency of a standardized algorithm/protocol for treatment of cerebral sinus thrombosis, which remains mostly at the discretion of experiences of treating physicians. In this study, the presently available treatment and diagnostic modalities with pros and cons of each of them were reviewed.

Iatrogenic fungal infections of central nervous system.

Iatrogenic fungal infections of the central nervous system had been considered a medical curiosity. Generally, they are a rare isolated complication of neurosurgical procedures, but periodically these infections are observed in larger populations as a result of exposure to contaminated materials during diagnostic or therapeutic procedures. In the last year, an epidemic of iatrogenic fungal central nervous system disease accompanied the use of fungal-contaminated compounded methylprednisolone distributed by one facility, heightening the attention given to this infectious disorder. As of May 6, 2013, 758 individuals from 20 US states have developed meningitis and/or spinal or paraspinal infection because of contaminated methylprednisolone from the New England Compounding Center in Framingham, Massachusetts, and 58 deaths have been reported. A total of 12 different fungi have been identified; Exserohilum rostratum, a filamentous environmental fungus rarely associated with human disease previously, has been the most commonly isolated pathogen. Meningitis has dominated the clinical presentation, accounting for more than half of the cases, but spinal and paraspinal infections, arachnoiditis, and stroke have also been observed. The diagnosis can be challenging as the organisms may be fastidious. An assay for ß-D-glycan has been proposed as an effective adjunctive test for E. rostratum infection. The current therapeutic recommendation is a 6 mg/kg dose of voriconazole every 12 h followed by liposomal amphotericin B. In some instances, surgical debridement and drainage may be necessary.

The neglected neglect: auditory neglect.

Whereas visual and somatosensory forms of neglect are commonly recognized by clinicians, auditory neglect is often not assessed and therefore neglected. The auditory cortical processing system can be functionally classified into 2 distinct pathways. These 2 distinct functional pathways deal with recognition of sound ("what" pathway) and the directional attributes of the sound ("where" pathway). Lesions of higher auditory pathways produce distinct clinical features. Clinical bedside evaluation of auditory neglect is often difficult because of coexisting neurological deficits and the binaural nature of auditory inputs. In addition, auditory neglect and auditory extinction may show varying degrees of overlap, which makes the assessment even harder. Shielding one ear from the other as well as separating the ear from space is therefore critical for accurate assessment of auditory neglect. This can be achieved by use of specialized auditory tests (dichotic tasks and sound localization tests) for accurate interpretation of deficits. Herein, we have reviewed auditory neglect with an emphasis on the functional anatomy, clinical evaluation, and basic principles of specialized auditory tests.

Thrombolysis in ischemic strokes with no arterial occlusion.

RATIONALE: Twelve million people develop ischemic stroke each year world over and 30-40% of them do not have arterial occlusions at presentation. Trials conducted to study the efficacy of thrombolytic drug reported better outcome with use of thrombolytic drug but none studied the subtypes of ischemic strokes specifically and adequately. The subgroups of patients with no arterial occlusion at presentation continue to receive thrombolytic therapy without proven benefit and with some risk. AIM: The aim of this article is to study whether intravenous thrombolysis with alteplase improves clinical outcome in ischemic stroke patients who do not have arterial occlusion at presentation. DESIGN: A retrospective medical record-based observational multicenter, multinational study. OUTCOMES: Primary outcome measure would be clinical outcome at three-months from stroke onset measured by modified Rankin Scale and National Institute of Health Stroke Scale. Secondary outcome measure will be frequency of intracerebral hemorrhage causing worsening of clinical deficit defined as increase in National Institute of Health Stroke Scale by >4.

Stand alone mechanical thrombectomy (with penumbra system) for acute ischemic stroke based on MR imaging: Single center experience.

BACKGROUND: There is dismal rate of recanalization following intravenous thrombolysis of large vessel occlusive ischemic stroke. Trials on use of mechanical clot retrievers in acute ischemic stroke have used time from onset and clinical deficit at presentation as the main indications for intervention. MATERIALS AND METHODS: Retrospective analysis of case records of acute stroke seen between May 2009 and October 2011 was done. It revealed 23 patients with acute ischemic stroke treated by mechanical thrombectomy using Penumbra system (PS). We used magnetic resonance (MR) imaging in correlation with clinical presentation to determine patients likely to benefit from recanalization and accordingly offered or at times deferred revascularization. A comparison of approach and outcomes was done with other relevant trials/reports. RESULTS: Recanalization was achieved in all but one patient. Median modified Rankin Scale (mRS) score at 90 days was 2. Good clinical outcome (mRS ≤ 2) was achieved in 56.5% compared with 25% in Penumbra pivotal trial and 36% in multi Mechanical Embolus Removal in Cerebral Ischemia (multi MERCI) trial. All cause mortality was 13.04%. Symptomatic intracerebral hemorrhage (ICH) occurred in two patients (8.6%). CONCLUSION: Analysis of our results suggests that PS is safe and effective (91.3%) in recanalizing cerebral vessels without concomitant thrombolytics.

An uncommon cause of intracerebral hemorrhage in a healthy truck driver.

OBJECTIVES: To describe a case and review literature for intracerebral hemorrhage caused by migraine. DESIGN: Case report. SETTING: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. PATIENT: A 54-year-old truck driver with a 2-year history of atypical headaches. RESULTS: A 54-year-old right-handed truck driver was seen in consultation with a 2-year history of atypical headaches.The headaches were dull, throbbing, gradually progressive,and limited over the left occipital area. They were accompanied by right visual field deficit, diplopia, and,at times, confusion. These headaches were notably different from the usual migraine headaches he had been having for more than 20 years. Brain imaging revealed left parieto-occipital lobar hemorrhage. Further investigations ruled out arteriovenous malformations. He did not have any vascular risk factors, including hypertension. Migraine-associated intracerebral hemorrhage was considered to be the most likely diagnosis. CONCLUSIONS: Intracerebral hemorrhage associated with migraine is believed to result from vasoconstriction leading to ischemia of the walls of blood vessels, making them leaky and porous. It is important to be aware of this phenomenon because vasoactive medications used to treat migraine can further aggravate the vasoconstriction and hence the intracerebral bleed.

Pediatric holohemispheric developmental venous anomaly: definitive characterization by 3D susceptibility weighted magnetic resonance angiography.

We present a case of an incidentally discovered holohemispheric developmental venous anomaly (DVA) in a 12 year old, conclusively characterized by 3D T2* multi-echo sequence susceptibility weighted angiographic imaging (SWAN). For the evaluation of head trauma, abnormal right intraparenchymal and periventricular vascularity was identified by a non contrast head CT scan. Conventional MRI sequences revealed prominent veins with findings suspicious of a DVA. A definitive diagnosis was made by identifying angiographic features typical for DVA by augmented susceptibility weighted angiographic imaging. Using this sequence the entire hemispheric extent of the anomaly without complicating features was definitively characterized, negating the need for a catheter based angiographic study. A holohemispheric DVA in a child to our knowledge has not been previously described.